Berberin inflamasyon baskılanması ve apoptoz indüksiyonu ile Caco-2 kolorektal adenokarsinom hücrelerinde 5-florourasil'in terapötik etkisini arttırır

Yıl 2023, Cilt: 48 Sayı: 4, 1238 - 1247, 29.12.2023

Seyma Oncu Merve Becit-kizilkaya Serkan Şen Fatma Özlem Kargın Solmaz Sefa Çelik

https://doi.org/10.17826/cumj.1344952

Öz

Amaç: Bu çalışma, berberin (BBR) ile kemoterapinin omurgasını oluşturan 5-fluorourasil (5FU)’in Caco-2 kolorektal adenokarsinoma hücreleri üzerinde sinerjik etki gösterip göstermediğini ve olası mekanizmalarını araştırmayı amaçlamaktadır.
Gereç ve Yöntem: Hücre canlılığı MTT yöntemiyle ve kombinasyon indeksi (CI) Chou-Talalay yöntemiyle belirlendi. Apoptoz ve inflamasyonla ilişkili proteinlerin (Bcl-2, p53, IL-6, TNF-α, MMP-9) konsantrasyonları ELISA ile ölçüldü.
Bulgular: BBR ve 5FU’nun IC50 değerleri 24 saat için 280 µM ve 20 mM olarak bulundu. Kombinasyon tedavi, her ikisinin de IC50 konsantrasyonlarında daha belirgin olmak üzere, sinerjik sitotoksik etki gösterdi (CI= 0.143). 5FU+BBR, Bcl-2’yi azaltarak ve p53’ü artırarak sinerjistik apoptotik etki gösterdi (5FU ile karşılaştırıldığında, Bcl-2 için 0.712 kat azalış ve p53 için 2.650 kat artış). Ayrıca, 5FU ile artan IL-6 ve TNF-α düzeyleri, 5FU+BBR tedavisi ile belirgin şekilde baskılandı (0.733 kat ve 0.485 kat). Ek olarak, 5FU ile tedavi edilen hücrelerde kontrol grubuna göre MMP-9 düzeylerinde anlamlı bir fark yokken, kombine tedavi MMP-9 düzeylerini belirgin şekilde (0.601 kat) azalttı.
Sonuç: Bulgular, BBR’nin 5FU ile birlikte kolorektal kanseri kemoterapisi için apoptoz indüksiyonu, inflamasyon baskılaması ve metastaz inhibisyonuyla muazzam potansiyelini ortaya koymaktadır.

Anahtar Kelimeler

Berberin (BBR), 5-fluorourasil (5FU), sinerjizm, Caco-2, apoptosis, MMP-9

Berberine enhances the therapeutic effect of 5-fluorouracil in Caco-2 colorectal adenocarcinoma cells by alleviating inflammation and inducing apoptosis

Öz

Purpose: This study aims to investigate whether berberine (BBR) and 5-fluorouracil (5FU), which forms the backbone of chemotherapy, have a synergistic effect on colorectal adenocarcinoma cells (Caco-2) and what mechanisms might be behind this.
Materials and Methods: Cell viability was determined by MTT and the combination index (CI) by Chou-Talalay method. Apoptosis and inflammation-related proteins (Bcl-2, p53, IL-6, TNF-α, MMP-9) were measured by ELISA.
Results: The IC50 values of BBR and 5FU were found to be 280 µM and 20 mM for 24 h. The combination treatment showed synergistic cytotoxicity, both of which were more pronounced at IC50 (CI=0.143). 5FU+BBR showed a synergistic apoptotic effect by decreasing Bcl-2 and increasing p53 (0.712-fold decrease in Bcl-2 and 2.650-fold increase in p53 compared to 5FU). The increase in IL-6 and TNF-α by 5FU was significantly suppressed by 5FU+BBR (0.733-fold and 0.485-fold). Although there was no significant difference in MMP-9 in 5FU compared to control, 5FU+BBR significantly decreased MMP-9 (0.601-fold).
Conclusion: The results show the enormous potential of BBR in combination with 5FU for the chemotherapy of colorectal carcinoma through apoptosis induction, inflammation inhibition and metastasis inhibition.

Anahtar Kelimeler

berberine (BBR), 5-fluorouracil (5FU), synergism, Caco-2, apoptosis, MMP-9

Kaynakça

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